WO2019183040A1 - ANTIBODIES BINDING TO VISTA AT ACIDIC pH - Google Patents

ANTIBODIES BINDING TO VISTA AT ACIDIC pH Download PDF

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WO2019183040A1
WO2019183040A1 PCT/US2019/022895 US2019022895W WO2019183040A1 WO 2019183040 A1 WO2019183040 A1 WO 2019183040A1 US 2019022895 W US2019022895 W US 2019022895W WO 2019183040 A1 WO2019183040 A1 WO 2019183040A1
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Prior art keywords
antibody
hvista
amino acid
e100ff
acid sequence
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PCT/US2019/022895
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English (en)
French (fr)
Inventor
Robert J. Johnston
Arvind Rajpal
Paul O. Sheppard
Luis Borges
Andrew Rankin
Keith Sadoon Bahjat
Alan Korman
Andy X. DENG
Linhui Julie SU
Ginger RAKESTRAW
Jason PINCKNEY
David CRITTON
Guodong Chen
Richard Y. Huang
Ekaterina G. DEYANOVA
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Five Prime Therapeutics, Inc.
Bristol-Myers Squibb Company
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Priority to JP2020550642A priority Critical patent/JP7510879B2/ja
Priority to CA3092589A priority patent/CA3092589A1/en
Application filed by Five Prime Therapeutics, Inc., Bristol-Myers Squibb Company filed Critical Five Prime Therapeutics, Inc.
Priority to EP19718001.1A priority patent/EP3768716A1/en
Priority to PE2020001432A priority patent/PE20210290A1/es
Priority to US16/982,277 priority patent/US20210017283A1/en
Priority to CN201980020908.XA priority patent/CN111971304A/zh
Priority to EA202092208A priority patent/EA202092208A1/ru
Priority to MX2020009786A priority patent/MX2020009786A/es
Priority to BR112020019083-7A priority patent/BR112020019083A2/pt
Priority to KR1020207029795A priority patent/KR20200135421A/ko
Priority to AU2019239747A priority patent/AU2019239747A1/en
Priority to SG11202008593PA priority patent/SG11202008593PA/en
Publication of WO2019183040A1 publication Critical patent/WO2019183040A1/en
Priority to IL277331A priority patent/IL277331A/en
Priority to CONC2020/0012415A priority patent/CO2020012415A2/es
Priority to JP2024000234A priority patent/JP2024050577A/ja

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • VISTA engages its counter-receptors and functions selectively at acidic pH, with little activity at
  • VISTA may thus suppress immune responses in acidic microenvironments, such as tumor beds or sites of inflammation, without perturbing cells circulating in blood or residing in non-inflamed, non-acidic tissues.
  • anti-VISTA antibodies can be engineered to selectively bind to VISTA at acidic pH, with little or no binding at physiological pH, mirroring VISTA’s own acidic pH selectivity. These acidic pH selective antibodies may offer desirable properties for treating diseases, such as cancer, relative to antibodies that bind VISTA at physiological pH.
  • the amino acid histidine has a pKa of about 6.5, meaning that at or below pH 6.5, histidine residues within proteins are often protonated and thus, positively charged, while at pH higher than pH 6.5 they are increasingly unprotonated and neutral in charge.
  • Tumor microenvironments and inflamed tissues are often acidic, and thus, VISTA proteins found in these microenvironments may be at least partially protonated at their histidine residues.
  • VISTA histidine protonation may affect the conformation, surface structure, and/or charge density of VISTA, which, in turn, may create pH-specific or pH-selective epitopes for both receptor-ligand interaction(s) and antibody binding.
  • Targeting VISTA with antibodies that bind at acidic pH but not neutral or physiological pH may prevent target- mediated drug disposition via circulating and lymphoid organ-resident myelomonocytic cells, improving antibody PK, receptor occupancy, and activity in tumor microenvironments.
  • Acidic pH-selective antibodies may also improve the specificity of VISTA antibodies for intratumoral, rather than circulating, target cells in the cases of therapeutic modalities such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and delivery of payloads (antibody-drug conjugates).
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • ADCP antibody-dependent cellular phagocytosis
  • CDC complement-dependent cytotoxicity
  • payloads antibody-drug conjugates
  • Figs.1A-C show that VISTA’s extracellular domain contains an exceptionally high frequency of histidine residues, that many of these histidine residues are conserved, and that at least some of these histidine residues may participate in receptor-ligand binding.
  • Fig.1A shows a graph of immunoglobulin domain-containing proteins, with the number of extracellular domain amino acid residues for each protein plotted on the x-axis, and the frequency of histidine residues within the extracellular domain for each protein plotted on the y-axis. The size of each data point corresponds to the total number of histidine residues in each protein’s extracellular domain.
  • Fig.1B shows the aligned amino acid sequences of the extracellular domains of human, cynomolgus macaque, and mouse VISTA. Signal peptide (Sig) and transmembrane domain (TMD) sequence locations are marked. Histidine residues conserved across all three species are shown in bold and underlined; histidine residues conserved across human and cynolmogus macaque are shown in bold only.
  • Fig.1C shows a model of the human VISTA immunoglobulindomain’s three-dimensional structure. Histidine residues are depicted as ball and stick traces.
  • Figs.2A-B show a model in which the histidine residues in VISTA’s extracellular domain confer counter-receptor selectivity for acidic pH rather than physiological pH.
  • Fig. 2A shows the equilibrium between the lack of, and the presence of, protonation of the pyrrole ammonium group (NH) in a histidine residue.
  • the pKa of histidine in solution is 6.5, indicating that histidine residues are more likely to be protonated at pH 6.5 and lower, and thus, positively charged, than at higher pH.
  • Fig.2B shows shows a model in which VISTA engages P-selectin glycoprotein ligand 1 (PSGL-1) or other counter-receptors and ligands (“VISTA-R”) selectively at acidic pH. Accordingly, antibody binding to VISTA’s extracellular domain at acidic pH rather than at physiological pH may be critical to inhibiting or modulating VISTA activity.
  • PSGL-1 P-selectin glycoprotein ligand 1
  • VISTA-R counter-receptors and ligands
  • Figs.4A-G show that VISTA selectively binds to leukocytes and to PSGL-1 at acidic pH, with little or no binding at neutral pH, and that this binding can be blocked by an anti- VISTA antibody.
  • Fig.4A on the left shows representative histograms of fluorescently- conjugated recombinant VISTA multimer binding to activated human CD4+ T cells. From darker gray to lighter, the filled histograms depict binding at pH 7.0, 6.5, 6.4, 6.3, 6.1, and 6.0. Some histograms are labeled with their corresponding pH. Non-VISTA control multimer binding at pH 6.0 is shown as the unfilled histogram.
  • Fig.4B shows representative histograms of recombinant VISTA multimer binding to peripheral blood mononuclear cells (PBMC) at pH 6.0 and pH 7.4. From darker gray to lighter, the filled histograms depict binding at pH 6.0 to CD19+ B cells, CD4+ T cells, CD8+ T cells, CD56+ NK cells, and CD14+ monocytes. The unfilled, solid border and dotted border histograms depict binding at pH 7.4 to total PBMC lymphocytes and monocytes respectively.
  • PBMC peripheral blood mononuclear cells
  • Fig.4C shows representative recombinant VISTA multimer binding to activated human CD4+ T cells in the presence of an anti-VISTA blocking antibody (squares) or a non-VISTA-specific isotype-matched control antibody (circles). Antibody concentrations are plotted on log scale. Non-linear regressions are also shown. The triangle depicts the background signal from activated human CD4+ T cells that were not stained with recombinant VISTA multimers.
  • Fig.4D shows representative two- dimensional flow cytometry plots of recombinant VISTA multimer binding at pH 6.0 to heparan sulfate-deficient Chinese Hamster Ovary (CHO) cells (line pGSD-677, American Type Culture Collection) that were transfected to express human PSGL-1. Multimer binding was performed in the presence and absence of the anti-VISTA blocking antibody shown in Fig.4C. Cells left unstained by recombinant VISTA multimers are shown as a control.
  • Figs.5A-D show that VISTA mediates T cell suppression and cell : cell adhesion preferentially at acidic pH, and that both effects can be reversed with an anti-VISTA blocking antibody.
  • Fig.5A shows representative cell : cell conjugate formation at pH 6.0 and 7.0 between 293T cells expressing hVISTA or vector control (plotted on the y-axes) and CHO cells endogenously expressing cell surface heparan sulfate on the x-axes.
  • Fig.5B is a graph of the frequency of cell conjugates formed at pH 6.0 between the same cells in the presence of an anti-VISTA blocking antibody, an anti-VISTA non-blocking antibody, or isotype-matched non-VISTA-specific control antibodies.
  • Fig.5C shows representative plots of the luciferase activity generated by Jurkat (human T cell line) cells expressing an NFkB luciferase reporter after co-culture at various pH with 293T cells expressing h VISTA and a single-chain variable fragment of the anti-human T cell receptor agonist antibody OKT3 (“artificial antigen-presenting cells”).
  • An anti-VISTA blocking antibody (squares) or an isotype-matched non-VISTA-specific control antibody (circles) were added to the co- cultured cells.
  • Fig.5D the data shown in Fig.5A are plotted as fold-increase of the luciferase signal with anti-VISTA antibody treatment relative to control (“effect size”).
  • Figs.6A-G show that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and can recycle to and from the cell surface via endosomal trafficking.
  • Fig.6A shows co-localization of VISTA, Rab5 (early endosome marker), Rab7 (late endosome marker), and Rab11 (recycling endosome marker) within 293T cells expressing human VISTA.
  • Fig.6B shows co-localization of VISTA and Rab11 within human monocytes. Intracellular VISTA is co-localized with Rab11+ recycling endosomes.
  • a non-VISTA-binding control antibody of the same isotype as the VISTA antibody (“cAb”) does not detectably bind the monocytes.
  • Figs.7A-F show how anti-VISTA antibody variant libraries were designed and screened in order to obtain acidic pH-selective antibodies.
  • Fig.7A shows amino acid substitutions that were made in VH CDR 3 of the anti-human VISTA antibody clone P1- 061029 (abbreviated‘029) for creating an‘029 library for screening.
  • the libraries allowed substitutions for the negatively charged amino acids aspartate and glutamate as well as pH-responsive histidine.
  • X H, D or E. Bracketed sequences were removed from synthesis to avoid introducing liabilities.
  • Fig.7B shows the procedure by which the‘029 library is iteratively screened and selected for acidic pH-selective antibody variants. R denotes selection round.
  • Fig.7C shows representative two-dimensional flow cytometry plots data showing the variant pool after 9 rounds of selection. VISTA binding is plotted on the y-axis, and variant antibody expression is plotted on the x-axis. Binding data at various antibody concentrations and pH are shown.
  • Fig.7D shows a diagram of P1-061029 and its progeny clones binding to human VISTA at pH 6.0 and 7.4.
  • Fig.7E shows a diagram of the off-rates of P1-061029 and its progeny clones to human VISTA at pH 6.0.
  • Fig.7F shows SPR binding data of the antibodies P1-068761, P1-068767 and P1-061029 to human VISTA at pH 6.0 and pH 7.4.
  • Figs.8A-F show acidic pH-selective cell binding, blocking, and effector activity of the VISTA antibodies P1-068761 and P1-068767.
  • Fig.8A and Fig.8B show the mean fluorescence intensity of the acidic pH-selective antibodies P1-068761 (Fig.8A) and P1- 068767 (Fig.8B) binding to Raji cells ectopically expressing human VISTA.
  • the cells were stained at approximately pH 6.0 (circles; highest curve in Fig.8A), 6.1 (squares; third highest curve), 6.2 (triangles; second highest curve), 6.4 (inverted triangles; fourth highest curve close to the pH 6.1 curve), 6.6 (diamonds; fourth curve from bottom), 7.0 (circles; third curve from bottom), 7.2 (squares; second curve from bottom), and 8.1 (unfilled triangles; bottom curve in Fig.8A). Binding was detected with a fluorescently conjugated anti-human IgG secondary antibody.
  • Fig.8C shows P1-068767 (circles) and an isotype-matched non-specific control antibody (triangles) binding to Raji cells ectopically expressing human VISTA at 3125 ng/mL at various pH.
  • Fig.8E shows the comparable blocking of recombinant VISTA multimer binding to activated human CD4+ T cells at pH 6.0 by P1- 061029 (squares), P1-068761 (triangles), and P1-068767 (inverted triangles), while a non- VISTA-specific control antibody (circles) did not block VISTA binding.
  • Fig.8F shows the reduced potency of P1-068761 (triangles) and P1-068767 (inverted triangles) in mediating antibody-dependent cell cytotoxicity (ADCC) at physiological pH.
  • P1-061029 squares
  • a non-VISTA-specific positive control antibody circles
  • a non-VISTA-specific negative control antibody are also shown.
  • NK cell specific lysis of target cells as a percentage of total target cells is plotted on the y-axis and antibody concentrations are plotted on the x-axis. Non-linear regressions are also shown.
  • Fig.9 shows enhanced pharmacokinetics (PK) of acidic pH-selective anti-VISTA antibodies in cynomolgus macaques.
  • the figure shows serum antibody concentrations over time in cynomolgus macaques treated VISTA antibody 2 (“control”, circles, see Fig.6C), VISTA antibody 3 (“acidic pH sensitive”, squares, see Fig.6C), or P1-068767 (triangles).
  • Figs.10A and 10B show the binding effects of mutations in the acidic pH-selective anti-VISTA antibodies‘761 and‘767.
  • Fig.10A shows kinetic binding data of P1-068761 reversion mutants at pH 7.4, pH 6.7 and pH 6.0 and the location of their reversion mutations relative to P1-068761.
  • Fig.10B shows kinetic binding data of P1-068767 reversion mutants at pH 7.4, pH 6.7 and pH 6.0 and the location of their reversion mutations relative to P1- 068767.
  • Figs.11A-C show epitope binning and mapping of various anti-VISTA antibodies.
  • Fig.11A shows the VISTA epitope competition for P1-068761 and P1-068767 compared to P1-061029 and VISTA antibody controls.
  • Fig.11B and Fig.11C show representations of the epitopes of all the residues for blocking hVISTA antibody (Fig.11B) as listed in Table 14 compared to a non-blocking hVISTA antibody (mAb1; Fig.11C).
  • Amino acid residues 66(H) and 162(A) are indicated to denote the orientation of the molecule. Histidine residues are in grey, and epitope residues are in black.
  • Figs.12A-C show imaged capillary isoelectric focusing (icIEF) data for the following: Fig.12A: P1-061029, Fig.12B: P1-068761, and Fig.12C: P1-068767.
  • Fig.13A and B show alignments of variable regions for‘029 and‘015 progeny clones.
  • Fig.13A shows the alignment of the amino acid sequences of the variable regions of ‘029 and its progeny clones.
  • Fig.13B shows the alighment of the amino acid sequences of the variable regions of‘015 and its progeny clones.
  • Fig.14 shows an alignment of VH sequences of P1-068761 with and without K16R and T84A substitutions.
  • the double-underlined residues show positions 16 and 84 of the framework regions and the shaded portions show the CDRs.
  • Figs.15G and H show results for individual mice shown in Figs.15A-D.
  • Fig.15I VISTA knockout mice and wildtype littermates were implanted with MC38 tumors and treated with non-binding isotype-matched control antibodies (upper two curves (0/7 TF and 0/5 TF, marked with circles and downward triangles) or with a mouse PD-1 blocking antibody (lower two curves 0/5 TF and 5/8 TF, marked with squares and downward triangles).
  • Fig.15N shows human VISTA KI and wildtype littermate (WT) mouse serum antibody concentrations after intravenous injection of 5 mg/kg of P1-061029 (WT, downward triangles; KI, squares) or P1-068767 (WT, upward triangles; KI, diamonds).
  • the calculated serum mean residence times (MRT) for P1-061029 and P1-068767 in KI mice are estimated to be 4.1 and 71 hours respectively.
  • n 4 KI mice and 1-2 WT mice per antibody.
  • the calculated serum mean residence times (MRT) for VISTA.4 and P1-061029 are estimated to be 7.6 hours and 717 hours respectively.
  • n 1 macaque per antibody.
  • Figs.16A-C show representative histograms of intratumoral CD8+ T cell expression of PD-1 (Fig.16A), LAG-3 (Fig.16B), and TIM-3 (Fig.16C) 7 days after the start of treatment. Error bars depict the standard error of the mean.
  • Fig.17C shows antibody blockade of VISTA-Fc binding to CHO-PSGL-1 cells by VISTA.4 (upward triangles) and by the anti-PSGL-1 antibody KPL-1 (circles). These data are representative of two independent experiments. Error bars depict the standard error of the mean.
  • Figs.18A-E show representations of the co-crystal structure of P1-068767 Fab and hVISTA, or (in Fig.18E) non-blocking antibody VISTA.5 and hVISTA.
  • the VISTA IgV domain features an unusual, histidine-rich extension of its central ß-sheet.
  • the VISTA IgV domain was co-crystallized with the P1-068767 Fragment antigen-binding (Fab).
  • FIG. 18A shows VISTA IgV domain : P1-068767 Fab co-crystal structure.
  • Figure 18A shows the overall structure of the VISTA IgV domain in complex with the P1-068767 Fab (heavy chain, dark gray; light chain, light gray).
  • Figure 18B shows a superimposition of the VISTA and PD-L1 IgV domains. VISTA histidine residues are depicted in stick representation.
  • Figure 18B shows that VISTA’s IgV domain possesses an unusual histidine-rich ß-sheet extension.
  • Figure 18C shows the molecular surface of the P1-068767 epitope (light grey electrostatic surface) as revealed by the VISTA + P1-068767 crystal structure.
  • Figure 18C shows that blocking antibodies bind to VISTA’s histidine-rich ß-sheet extension.
  • Figure 18D shows an enlarged view of the interface between VISTA (grey ribbon cartoon, with epitope residues H121, H122, and H123 depicted in stick representation) and P1-068767 (depicted as an electrostatic surface with its residues E100 and D102 in stick representation).
  • Figure 18D shows that acidic pH-selective P1-068767 engages VISTA histidines with acidic residues.
  • Figure 18E shows that non-blocking antibody VISTA.5 binds in a different region of hVISTA from P1-068767.
  • Fig.19 shows the epitope of VISTA.4 as determined by MS-HDX (MS trace).
  • Fig.20 shows the location of the epitope of VISTA.4 in the amino acid sequence of hVISTA based on the data in Fig.19. Residues 57-68, 86-97, and 148-165, also highlighted in Fig.19, are depicted in lighter grey text and underlining in Fig.20.
  • Figs.21A and 21B show VISTA multimer binding to activated human CD4+ T cells at pH 6.0 in the presence of the antibodies VISTA.4 (triangles), VISTA.5 (squares), and a non-VISTA-binding (control, circles).
  • Figure 21B shows the blocking efficiency of each antibody relative to non-blocked T cells.
  • Fig.22 shows that antibodies that block VISTA binding at acidic pH are functional.
  • Fig.23 shows the effects of VISTA.4 blockade on Jurkat T cell activation (by measurement of NF-kB inhibition) following co-culture with 293T-OKT3-VISTA cells at different pH.
  • Fig.24 shows effects of pH on VISTA suppression of human CD4+ T cells.
  • Cells were stimulated at the indicated pH with plate coated OKT3 and VISTA-Fc in the presence of VISTA.4 (upward triangles), VISTA.5 (downward triangles), or a non-VISTA-binding antibody (antibody control, squares).
  • VISTA.4 upward triangles
  • VISTA.5 downward triangles
  • a non-VISTA-binding antibody antibody control, squares
  • Cells stimulated with plate-coated OKT3 and control IgG VISTA control, black circles
  • OKT3 no OKT3, grey diamond
  • FIGs.25 A-E show that VISTA : PSGL-1 binding specificity is determined by histidine and sulfotyrosine residues.
  • human PSGL-119-mer-Fc recombinant proteins were produced in cells with or without sialyl lewis X decoration (SLX+ and SLX- respectively).
  • BLI binding magnitudes at pH 6.0 (white) and 7.4 (black) are shown for VISTA-Fc and P-selectin-Fc as indicated. Data are representative of a single independent experiment.
  • Figs.25C- 25D human VISTA-Fc recombinant proteins were produced with the histidine residues at positions 153-155 left intact (WT VISTA) or replaced by alanine (H2A mutant), aspartic acid (H2D mutant), or arginine (H2R mutant).
  • Fig.25C shows BLI binding magnitudes for wildtype and mutant VISTA-Fc proteins binding to captured PSGL-1 at pH 6.0 and 7.4. These data are representative of a single experiment.
  • Fig.25D shows VISTA-Fc binding to CHO-PSGL-1 cells at pH 6.0 of WT VISTA (circles), H2A mutant (squares), H2D mutant (downward triangles), and H2R mutant (grey upward triangles), as well as a control
  • an“isolated” molecule is a molecule that has been removed from its natural milieu.
  • the term“isolated” does not necessarily reflect the extent to which the molecule has been purified.
  • polypeptide refers to a polymer of amino acid residues, and is not limited to a minimum length.
  • A“protein” may comprise one or more polypeptides.
  • Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are encompassed by the definition.
  • the terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like.
  • a“polypeptide” or“protein” refers to a polypeptide or protein, respectively, which includes modifications, such as deletions, additions, and substitutions (generally conservative in nature), to the native sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site- directed mutagenesis, or may be accidental, such as through mutations of hosts that produce the proteins or errors due to PCR amplification.
  • a protein may comprise two or more polypeptides.
  • VISTA is an abbreviation for the V-domain immunoglobulin-containing suppressor of T-cell activation protein, which is a member of the B7 family of immune checkpoint regulators. VISTA is also known as the PD-1 homolog (PD1H), B7-H5, C10orf54, differentiation of ESC-1 (Dies-1), platelet receptor Gi24 precursor, and death domain 1 ⁇ (DD1 ⁇ ).
  • PD1H PD-1 homolog
  • B7-H5 B7-H5
  • C10orf54 C10orf54
  • differentiation of ESC-1 Dies-1
  • platelet receptor Gi24 precursor DD1 ⁇
  • DD1 ⁇ death domain 1 ⁇
  • the term“hVISTA” or“huVISTA” herein refers to the human VISTA protein.
  • the amino acid sequence of hVISTA, including its signal peptide is provided in SEQ ID NO:1, while the sequence without the signal peptide is provided in SEQ ID NO:2.
  • the extracellular domain or“ECD” of VISTA or the“VISTA- ECD” refers to the portion of the VISTA protein that is located in the extracellular space, which, in the case of hVISTA, comprises the amino acids 1-162 of SEQ ID NO:2. (See also Fig.1B.)
  • The“IgV domain” portion of hVISTA comprises residues 5-135 of SEQ ID NO:2.
  • leader peptide or“leader sequence” refers to a sequence of amino acid residues located at the N terminus of a polypeptide that facilitates secretion of a polypeptide from a mammalian cell.
  • a leader sequence may be cleaved upon export of the polypeptide from the mammalian cell, forming a mature protein.
  • Leader sequences may be natural or synthetic, and they may be heterologous or homologous to the protein to which they are attached.
  • A“growth inhibitory agent” as used herein refers to a compound or composition that inhibits growth of a cell (such as a cell expressing VEGF) either in vitro or in vivo.
  • the growth inhibitory agent that can be administered in methods herein may be one that significantly reduces the percentage of cells (such as a cell expressing VEGF) in S phase.
  • growth inhibitory agents include, but are not limited to, agents that block cell cycle progression (at a place other than S phase), such as agents that induce G1 arrest and M- phase arrest.
  • the Abs may bind with a k on of 10 7 M -1 s -1 or higher.
  • an Ab may bind to the VISTA-ECD protein at a pH of 6.5 or less with a kon of 10 6 M -1 s -1 or higher, as measured, e.g., at 25°C or at 37°C.
  • an Ab may bind to the ECD of hVISTA at a pH of 6.5 or less with a k on of 10 6 M -1 s -1 or higher, as measured, e.g., at 25°C or at 37°C.
  • an Ab may bind to the VISTA-ECD protein at a pH of 6.5 or less with a KD of 10 -9 M or less as well as with a koff of 10 -5 s -1 or less, 10 -4 s -1 or less, 10 -3 s -1 or less, 10 -2 s -1 or less, or 10 -1 s -1 or less, as measured, e.g., at 25°C or at 37°C.
  • an Ab may bind to the VISTA-ECD protein at a pH of 6.5 or less with a KD of 10 -7 M or less as well as with a koff of 10 -5 s -1 or less, 10 -4 s -1 or less, 10 -3 s -1 or less, 10 -2 s -1 or less, or 10 -1 s -1 or less, as measured, e.g., at 25°C or at 37°C, and a kon of 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher, as measured, e.g., at 25°C or at 37°C.
  • an Ab binds to a conformational epitope that comprises, or is present within, residues 103-111 of SEQ ID NO: 2 and 136-146 of SEQ ID NO:2 for human VISTA. In certain embodiments, an Ab binds to a conformational epitope that comprises, or is present within, residues 24-36, 54-65, and 100-102 of SEQ ID NO:2 for human VISTA. In certain embodiments, an Ab binds to a conformational epitope that comprises amino acid residues in the FG loop of human VISTA. In some embodiments, an Ab binds to a polypeptide comprising amino acid residues 35 to 127 and/or 37-125 of SEQ ID NO: 2.
  • Some of the above antibodies may show differential binding affinity for VISTA-ECD proteins depending upon pH.
  • Certain Abs specifically binding to a VISTA-ECD protein in acidic conditions e.g., at pH 6.5 or less, also specifically bind the VISTA-ECD protein at neutral and/or alkaline pH with similar affinity (i.e. they are“pan binders”).
  • some such Abs may bind to the VISTA-ECD protein with a KD of 10 -7 M or less at both pH 6.5 and at pH 7.0 (at a constant temperature, e.g., of 25°C or at 37°C) such that the KD at pH 6.5 is within 1.5-fold of the K D at pH 7.0.
  • Certain Abs specifically binding to a VISTA-ECD protein in acidic conditions may bind the VISTA-ECD protein at neutral, physiological, and/or alkaline conditions with lower affinity (“pH sensitive binders” or“pH sensitive Abs”).
  • Certain Abs specifically binding to a VISTA-ECD protein in acidic conditions e.g., at pH 6.5 or less, may have non significant, e.g., nearly undetectable, binding to the VISTA-ECD protein in neutral, physiological and/or alkaline conditions.
  • Abs may bind to the VISTA-ECD protein with a KD of 10 -8 M or less at pH 6.5 and with a KD of more than 10 -8 M at pH 7.0 and/or pH 7.4.
  • Abs may bind to the VISTA-ECD protein with a K D of 10 -8 M or less at pH 6.5 and with a K D at pH 7.0 and/or pH 7.4 that is more than 1.5-fold higher than that at pH 6.5.
  • a pH sensitive Ab that specifically binds to the VISTA-ECD protein with a KD that is at least 1.5 fold, 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold, 300 fold, 500 fold, 1000 fold, or 5000 fold lower at pH 6.5 than at pH 7.0 (at a constant temperature, e.g., of 25°C or at 37°C).
  • an Ab specifically binds to a VISTA-ECD protein with a k off that is lower in acidic conditions relative to that in neutral, physiological, or alkaline conditions.
  • an Ab is provided that binds to the VISTA-ECD protein in acidic conditions with a koff that is at least 1.5 fold, 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold, or 1000 fold lower at pH 6.5 than the k off at pH 7.0 and/or pH 7.4, as measured, e.g., at 25°C or at 37°C. In other words, the off-rate is slower at acidic pH than at neutral pH.
  • an Ab specifically binds to a VISTA-ECD protein with a koff rate that is at least 1.5 fold, 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold or 1000 fold lower at pH 6.0, relative to pH 7.4, as measured, e.g., at 25°C or at 37°C.
  • an Ab is provided that binds to the VISTA-ECD protein with a k off that is at least 1.5 fold, 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold or 1000 fold lower at pH 6.0-6.5 than the koff at pH 7.0-7.4, as measured, e.g., at 25°C or at 37°C.
  • an Ab that specifically binds to a VISTA-ECD protein with a kon that is higher in acidic conditions relative to neutral, physiological, or alkaline conditions is provided that binds to a VISTA-ECD protein in acidic conditions with a k on that is at least 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold, or 1000 fold higher at pH 6.5 than the kon at pH 7.0 and/or pH 7.4, as measured, e.g., at 25°C or at 37°C.
  • an Ab specifically binds to aVISTA-ECD protein with a k on that is at least 2 fold, 5 fold, 10 fold, 20 fold, 50 fold, 100 fold or 1000 fold higher at pH 6.0 than at pH 7.0 and/or pH 7.4, as measured, e.g., at 25°C or at 37°C.
  • an Ab specifically binds to a VISTA-ECD protein at a pH at which at least one histidine residue, e.g., His 98 in SEQ ID NO: 1, is protonated. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein at a pH at which most histidine residues in the ECD are protonated, which is expected to be pH 6.5 or less, e.g., between pH 6.0 and pH 6.5.
  • an Ab may bind to an epitope comprising one of the regions of SEQ ID NO:2 described above, and also may have pan binding or pH sensitive or pH selective binding properties as described above, as shown by one or more of the behaviors of its KD, koff, or kon at different pH’s.
  • the Ab may be, for example, a full length antibody (i.e., comprising a full length heavy chain (with or without C-terminal lysine) and a full length light chain), or an antigen binding fragment such as a Fab fragment, a Fab’ fragment, (Fab’)2 fragment, an scFv fragment, an Fv fragment, or the Ab may be a chimeric, humanized, or human antibody, or the Ab may be a bispecific or multispecific antibody.
  • a full length antibody i.e., comprising a full length heavy chain (with or without C-terminal lysine) and a full length light chain
  • an antigen binding fragment such as a Fab fragment, a Fab’ fragment, (Fab’)2 fragment, an scFv fragment, an Fv fragment, or the Ab may be a chimeric, humanized, or human antibody, or the Ab may be a bispecific or multispecific antibody.
  • SPR surface plasmon resonance
  • An exemplary SPR assay comprises capturing one or several antibodies on a CM4 sensor chip with immobilized capture reagent (e .g., using Biacore® anti-human Fc capture kit, GE Healthcare catalog # BR-1008-39, or Biacore® anti-mouse capture kit, GE Healthcare catalog #BR-1008-39), and flowing VISTA antigen as analyte in a concentration series to determine binding kinetics and affinities in a running buffer with desired pH.
  • immobilized capture reagent e .g., using Biacore® anti-human Fc capture kit, GE Healthcare catalog # BR-1008-39, or Biacore® anti-mouse capture kit, GE Healthcare catalog #BR-1008-39
  • VISTA is injected at two to five concentrations in the range of 0.1 nM to 500 nM (e.g., 0.1 nM, 1 nM, 10 nM, 100 nM, 500 nM) with a flow rate of 30 uL/min, up to four minutes association time and up to ten minutes dissociation time. Between binding cycles, the capture surface is regenerated following the
  • Abs e.g., human IgG
  • hVISTA Abs against hVISTA are serially diluted from approximately 20 ⁇ g/mLand incubated with the re-suspended cells for 30 minutes at 4 °C. Cells are then washed twice with the same buffers, maintaining the desired pH, e.g., pH at 6.0 or 7.4, and incubated with a fluorophore-conjugated secondary antibody that recognizes the primary antibody (e.g., human IgG) and is stable at reduced pH. Cells are then washed as before and acquired immediately, without fixation, on a BD Fortessa or other flow cytometer. The affinity of an Ab for a VISTA ECD polypeptide may be determined as described in the Examples.
  • Abs that bind to hVISTA ECD block binding of hVISTA to its binding partner (e.g., a VISTA receptor), e.g., on cells. Inhibition or blocking may be 100% or at least 99%, 95%, 90%, 85%, 80%, 75%, or 50%.
  • an Ab binds to a VISTA-ECD protein at acidic pH, e.g., pH 6.5 or less, and inhibits binding of VISTA to its binding partner by at least 50%, such as by at least 75%, 80%, 85%, 90%, 95%, or 100%.
  • Certain Abs specifically bind to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH within a range of pH 5.0-pH 7.0.
  • Certain Abs specifically bind to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH within a range of pH 5.5-pH 6.5. Certain Abs specifically bind to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH within a range of pH 6.0-6.5. Inhibition of binding can be determined as described in the Examples.
  • Inhibition of binding to a VISTA binding partner can be determined by measuring the inhibition of binding of VISTA (or VISTA ECD or VISTA IgV domain or VISTA positive cells), to cells to which VISTA binds, e.g., T cells (e.g., CD4+T cells, CD8+ T cells, either activated or not), NK cells, or other cells to which VISTA binds, in the presence and absence of the antibody.
  • T cells e.g., CD4+T cells, CD8+ T cells, either activated or not
  • NK cells e.g., CD4+T cells, CD8+ T cells, either activated or not
  • the Abs described herein may trigger or enhance an immune response, such as an antigen-specific immune response.
  • the Abs stimulate T cell activity, particularly at acidic pH such as is found in tumor
  • Activity of anti-VISTA Abs can also be shown in monocyte assays, ADCC assays, and ADCP assays, particularly at acidic pH such as is found in tumor microenvironments.
  • Abs that bind preferentially to hVISTA (ECD) at acidic pH (e.g., in acidic conditions) relative to physiological pH or neutral pH.
  • an anti-hVISTA Ab comprises a heavy chain variable region (“VH”) comprising VH CDR1, CDR2 and/or CDR3 of any of the anti-hVISTA Abs provided herein.
  • VH heavy chain variable region
  • an anti-hVISTA Ab comprises a VH comprising the VH CDR1, CDR2 and CDR3 of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VH comprising VH CDR1, CDR2 and/or CDR3 of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1-068757, P1- 068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1- 068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1- 069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1- 068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N,
  • an anti-hVISTA Ab comprises a VLcomprising VL CDR1, CDR2 and CDR3 of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VLcomprising VL CDR1, CDR2 and CDR3 of one of P1- 061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1- 068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1- 069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1- 061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1- 068761_E56N, P1-068761_E55A_E56
  • VL CDR1, CDR2, and CDR3 of each of these species comprise amino acid positions 24-35 (VL CDR1), 51-57 (VL CDR2), and 90-98 (VL CDR3), of the VL sequences for each of the above antibody species provided in the Sequence Table below.
  • the CDRs are also underlined and in bold on each of those sequences.
  • an anti-hVISTA Ab comprises a VH comprising VH CDR1, CDR2 and/or CDR3 of any of the anti-hVISTA Abs provided herein and a VL comprising CDR1, CDR2 and/or CDR3 of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VH comprising VH CDR1, CDR2 and CDR3 of any of the anti-hVISTA Abs provided herein and a VL comprising CDR1, CDR2 and CDR3 of any of the anti-hVISTA Abs provided herein.
  • an anti- hVISTA Ab comprises a VH comprising VH CDR1, CDR2 and/or CDR3 of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1-068757, P1-068759, P1-068761, P1- 068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1- 069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1- 069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N
  • an anti-hVISTA Ab may comprise:
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 061029 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-061029;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 061015 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-061015;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068757 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068757;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068759 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068759;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068763 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068763;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068765 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068765;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068769 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068769;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068771 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068771;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068775 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068775
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069059 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069059;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069063 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069063;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069065 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069065;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069069 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069069;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069071 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069071;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069073 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069073;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069075 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069075;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 069077 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-069077;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068736 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068736;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068738 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068738;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068740 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068740;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068742 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068742;
  • aa a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068744 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068744;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068754 and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068754;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068761_E56N and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068761_E56N;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068761_E55A_E56N and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068761_E55A_E56N;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068761_E30D and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068761_E30D;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068761_E30D_E55A and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068761_E30D_E55A;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068761_H100G_E100fF and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068761_H100G_E100fF;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068761_E30D_E100fF and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068761_E30D_E100fF;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068761_E56N_E100fF and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068761_E56N_E100fF;
  • a VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068767_E30D and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068767_E30D;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 068767_E30D_E55A and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 068767_E30D_E55A;
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1-068767_E55A_E100fF and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068767_E55A_E100fF;
  • (nnn) a VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and
  • VH comprising the amino acid sequence of the VH CDR1, CDR2 and CDR3 of P1- 061029_Y32E_F100fE and a VL comprising the VL CDR1, CDR2 and CDR3 of P1- 061029_Y32E_F100fE.
  • the Sequence Table below provides the heavy and light chain variable region sequences and full length heavy and light chain sequences of the antibodies listed above with an IgG1.3 heavy chain constant region (unless a different HC constant region is noted in the table) and notes the locations of their VH CDR1, CDR2, and CDR3 and VL CDR1, CDR2, and CDR3 by amino acid residue and with bolding and underlining of the CDRs in each VH and VL sequence.
  • VH CDR1 of P1-061029 comprises amino acids 26-35 of SEQ ID NO: 67
  • VH CDR2 comprises amino acids 50-66 of SEQ ID NO: 67
  • VH CDR3 comprises amino acids 99-110 of SEQ ID NO: 67, and so forth, as noted by the bolded and underlined amino acids of SEQ ID NO: 67 shown in the Sequence Table.
  • an anti-hVISTA Ab comprises a VH comprising the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein.
  • the individual VH sequences for particular antibody species provided herein are listed in the Sequence Table.
  • an anti-hVISTA Ab comprises a VH comprising the amino acid sequence of the VH of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1- 068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1- 068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1- 069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1- 068736, P1-068738, P1-068740, P1-068742, P1-06874
  • an anti-hVISTA Ab comprises the VH of any of antibodies P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1- 068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1- 069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1- 061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1- 068761_E56N, P1-068761_E55A_E56N, P1-068761_E55A_E56N, P1-068761_
  • an anti-hVISTA Ab comprises the VH of any of antibodies P1-061029 or its progeny such as , P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1- 068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1- 069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1- 069077, P1-068766, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1- 068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1- 068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E
  • an anti-hVISTA Ab comprises a VH CDR1, CDR2, and CDR3 comprising the amino acid sequences of the VH CDRs of any of the anti-hVISTA Abs provided herein and comprises a VH that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VH comprising an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of the VH of P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1- 068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1- 069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1- 068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-0
  • substitutions in the framework regions of the VH sequence such as 1, 2, 3, 4, or 5 conservative substitutions, or such as one or both of K16R and/or T84A substitutions in P1- 061029 or its progeny.
  • an anti-hVISTA Ab comprises a VH consisting of the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VH that consists of the amino acid sequence of the VH of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1- 068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1- 069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1- 068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068
  • an anti-hVISTA Ab comprises a VL comprising the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VL comprising the amino acid sequence of the VL of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1-068757, P1- 068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1- 068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1- 069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1- 068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752
  • an anti-hVISTA Ab comprises a VL CDR1, CDR2, and CDR3 comprising the amino acid sequences of the VL CDRs of any of the anti-hVISTA Abs provided herein and comprises a VL that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VL of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VL comprising an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of the VL of P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1- 068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1- 069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1- 069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752
  • an anti-hVISTA Ab comprises a VL consisting of the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein.
  • an anti-hVISTA Ab comprises a VL that consists of the amino acid sequence of the VL of P1-061029 or P1-061015 or progeny thereof, such as P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1- 068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1- 069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1- 068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068
  • an anti-hVISTA Ab comprises a VH comprising the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein and comprises a VL comprising the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein.
  • the VH of the antibody is that of P1-061029, P1- 068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1- 068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1- 069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1- 068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1- 068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_
  • VH comprising the amino acid sequence of the VH of P1-069071 and a VL
  • VH comprising the amino acid sequence of the VH of P1-069073 and a VL
  • VH comprising the amino acid sequence of the VH of P1-068752 and a VL comprising the amino acid sequence of the VL of P1-068752;
  • VH comprising the amino acid sequence of the VH of P1-068754 and a VL
  • VH comprising the amino acid sequence of the VH of P1- 068761_E30D_H100G and a VL comprising the amino acid sequence of the VL of P1-068761_E30D_H100G;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E30D_E56N and a VL comprising the amino acid sequence of the VL of P1- 068761_E30D_E56N;
  • (tt) a VH comprising the amino acid sequence of the VH of P1-068761_E56N_E100fF and a VL comprising the amino acid sequence of the VL of P1- 068761_E56N_E100fF;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E32Y_E56N and a VL comprising the amino acid sequence of the VL of P1- 068761_E32Y_E56N;
  • VH comprising the amino acid sequence of the VH of P1-068767_E55A_E100fF and a VL comprising the amino acid sequence of the VL of P1- 068767_E55A_E100fF;
  • VL comprising the amino acid sequence of the VL of P1-068757;
  • VH comprising the amino acid sequence of the VH of P1-068765 modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068765;
  • VH comprising the amino acid sequence of the VH of P1-068767 modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068767;
  • VH comprising the amino acid sequence of the VH of P1-068769 modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068769;
  • VH comprising the amino acid sequence of the VH of P1-068771 modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068771;
  • VL comprising the amino acid sequence of the VL of P1-069065;
  • VL comprising the amino acid sequence of the VL of P1-069071;
  • VL comprising the amino acid sequence of the VL of P1-069073;
  • VH comprising the amino acid sequence of the VH of P1-068761_E55A modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E55A;
  • a VH comprising the amino acid sequence of the VH of P1-068761_H100G modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_H100G
  • a VH comprising the amino acid sequence of the VH of P1-068761_E56N modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E56N;
  • VH comprising the amino acid sequence of the VH of P1-068761_E55A_E56N modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E55A_E56N;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E30D_E55A modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E30D_E55A;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E56N_H100G modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E56N_H100G;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E30D_E56N modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E30D_E56N;
  • VH comprising the amino acid sequence of the VH of P1-068761_E100fF modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E100fF;
  • VH comprising the amino acid sequence of the VH of P1-068761_E55A_E100fF modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E55A_E100fF;
  • VH comprising the amino acid sequence of the VH of P1-068761_E56N_E100fF modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E56N_E100fF;
  • VH comprising the amino acid sequence of the VH of P1-068761_E32Y modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E32Y;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E32Y_E55A modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E32Y_E55A;
  • VH comprising the amino acid sequence of the VH of P1-068761_E32Y_E56N modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E32Y_E56N;
  • VH comprising the amino acid sequence of the VH of P1- 068761_E30D_E32Y modified by K16R and/or T84A substitutions
  • VL comprising the amino acid sequence of the VL of P1-068761_E30D_E32Y
  • VH comprising the amino acid sequence of the VH of P1- 068761_E32Y_E100fF modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068761_E32Y_E100fF;
  • (tt) a VH comprising the amino acid sequence of the VH of P1-068767_D102V modified by K16R and/or T84A substitutions, a VL comprising the amino acid sequence of the VL of P1-068767_D102V;
  • VH comprising the amino acid sequence of the VH of P1-068767_E30D modified by K16R and/or T84A substitutions, and a VL comprising the amino acid sequence of the VL of P1-068767_E30D;
  • (ccc) a VH comprising the amino acid sequence of the VH of P1-068767_E100fF modified by K16R and/or T84A substitutions and a VL comprising the amino acid sequence of the VL of P1-068767_E100fF;
  • VH comprising the amino acid sequence of the VH of P1- 061029_F100fE_V102D modified by K16R and/or T84A substitutions and a VL comprising the amino acid sequence of the VL of P1-061029_F100fE_V102D;
  • (fff) a VH comprising the amino acid sequence of the VH of P1-061029_F100fE modified by K16R and/or T84A substitutions and a VL comprising the amino acid sequence of the VL of P1-061029_F100fE;
  • VH comprising the amino acid sequence of the VH of P1-061029_V102D modified by K16R and/or T84A substitutions and a VL comprising the amino acid sequence of the VL of P1-061029_V102D;
  • a VH comprising the VH CDRs of the VH of P1-061029 and a VL comprising the VL CDRs of P1-061029 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061029;
  • a VH comprising the VH CDRs of the VH of P1-061015 and a VL comprising the VL CDRs of P1-061015 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061015;
  • a VH comprising the VH CDRs of the VH of P1-068767 and a VL comprising the VL CDRs of P1-068767 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068767;
  • VH comprising the VH CDRs of the VH of P1-068775 and a VL comprising the VL CDRs of P1-068775 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068775;
  • a VH comprising the VH CDRs of the VH of P1-069063 and a VL comprising the VL CDRs of P1-069063 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069063;
  • a VH comprising the VH CDRs of the VH of P1-069065 and a VL comprising the VL CDRs of P1-069065 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069065; (q) a VH comprising the VH CDRs of the VH of P1-069067 and a VL comprising the VL CDRs of P1-069067 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069067;
  • a VH comprising the VH CDRs of the VH of P1-069069 and a VL comprising the VL CDRs of P1-069069 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069069;
  • VH comprising the VH CDRs of the VH of P1-069071 and a VL comprising the VL CDRs of P1-069071 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069071;
  • VH comprising the VH CDRs of the VH of P1-069073 and a VL comprising the VL CDRs of P1-069073 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069073;
  • a VH comprising the VH CDRs of the VH of P1-069075 and a VL comprising the VL CDRs of P1-069075 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069075;
  • a VH comprising the VH CDRs of the VH of P1-069077 and a VL comprising the VL CDRs of P1-069077 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-069077;
  • a VH comprising the VH CDRs of the VH of P1-068736 and a VL comprising the VL CDRs of P1-068736 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068736; (x) a VH comprising the VH CDRs of the VH of P1-068738 and a VL comprising the VL CDRs of P1-068738 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068738;
  • VH comprising the VH CDRs of the VH of P1-068740 and a VL comprising the VL CDRs of P1-068740 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068740;
  • a VH comprising the VH CDRs of the VH of P1-068742 and a VL comprising the VL CDRs of P1-068742 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068742;
  • a VH comprising the VH CDRs of the VH of P1-068744 and a VL comprising the VL CDRs of P1-068744 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068744; (bb) a VH comprising the VH CDRs of the VH of P1-068746 and a VL comprising the VL CDRs of P1-068746 and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068746; (cc) a VH comprising the VH comprising the
  • (gg) a VH comprising the VH CDRs of the VH of P1-068761_E55A and a VL comprising the VL CDRs of P1-068761_E55A and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E55A;
  • a VH comprising the VH CDRs of the VH of P1-068761_H100G and a VL comprising the VL CDRs of P1-068761_H100G and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_H100G;
  • VH comprising the VH CDRs of the VH of P1-068761_E56N and a VL comprising the VL CDRs of P1-068761_E56N and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1- 068761_E56N;
  • a VH comprising the VH CDRs of the VH of P1-068761_E55A_E56N and a VL comprising the VL CDRs of P1-068761_E55A_E56N and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E55A_E56N;
  • a VH comprising the VH CDRs of the VH of P1-068761_E30D and a VL comprising the VL CDRs of P1-068761_E30D and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E30D; (ll) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E55A and a VL comprising the VL CDRs of P1-068761_E30D_E55A and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to
  • a VH comprising the VH CDRs of the VH of P1-068761_E30D_H100G and a VL comprising the VL CDRs of P1-068761_E30D_H100G and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E30D_H100G;
  • VH comprising the VH CDRs of the VH of P1-068761_E30D_E56N and a VL comprising the VL CDRs of P1-068761_E30D_E56N and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E30D_E56N;
  • a VH comprising the VH CDRs of the VH of P1-068761_E32Y and a VL comprising the VL CDRs of P1-068761_E32Y and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E32Y;
  • Vv a VH comprising the VH CDRs of the VH of P1-068761_E32Y_E55A and a VL comprising the VL CDRs of P1-068761_E32Y_E55A and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068761_E32Y_E55A;
  • VH comprising the VH CDRs of the VH of P1-068767_D52N_D102V and a VL comprising the VL CDRs of P1-068767_D52N_D102V and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068767_D52N_D102V;
  • VH comprising the VH CDRs of the VH of P1-068767_E55A and a VL comprising the VL CDRs of P1-068767_E55A and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068767_E55A;
  • VH comprising the VH CDRs of the VH of P1-068767_E30D and a VL comprising the VL CDRs of P1-068767_E30D and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1- 068767_E30D; (jjj)a VH comprising the VH CDRs of the VH of P1-068767_E30D_E55A and a VL comprising the VL CDRs of P1-068767_E30D_E55A and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the V
  • (nnn) a VH comprising the VH CDRs of the VH of P1-068767_E100fF and a VL comprising the VL CDRs of P1-068767_E100fF and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068767_E100fF;
  • a VH comprising the VH CDRs of the VH of P1-068767_E30D_E100fF and a VL comprising the VL CDRs of P1-068767_E30D_E100fF and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-068767_E30D_E100fF; (ppp) a VH comprising the VH CDRs of the VH of P1-061029_F100fE_V102D and a VL comprising the VL CDRs of P1-061029_F100fE_V102D and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%
  • qqq a VH comprising the VH CDRs of the VH of P1-061029_F100fE and a VL comprising the VL CDRs of P1-061029_F100fE and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061029_F100fE;
  • (rrr) a VH comprising the VH CDRs of the VH of P1-061029_V102D and a VL comprising the VL CDRs of P1-061029_V102D and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061029_V102D;
  • (sss) a VH comprising the VH CDRs of the VH of P1-061029_Y32E and a VL comprising the VL CDRs of P1-061029_Y32E and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061029_Y32E; or
  • (ttt) a VH comprising the VH CDRs of the VH of P1-061029_Y32E_F100fE and a VL comprising the VL CDRs of P1-061029_Y32E_F100fE and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the VH and VL of P1-061029_Y32E_F100fE;
  • the VH and/or VL may differ from the sequence of each of the species (a) to (ttt) by the presence of 1, 2, 3, 4, or 5 amino acid substitutions, such as 1, 2, 3, 4, or 5 conservative substitutions.
  • the VH may comprise one or both of the K16R and T84A substitutions.
  • An anti-hVISTA Ab may comprise:
  • VH consisting of the amino acid sequence of the VH of P1-068752 and a VL consisting of the VL of P1-068752;
  • (tt) a VH consisting of the amino acid sequence of the VH of P1-068761_E56N_E100fF and a VL consisting of the amino acid sequence of the VL of P1- 068761_E56N_E100fF;
  • VH consisting of the amino acid sequence of the VH of P1- 068767_D52N_D102V and a VL consisting of the amino acid sequence of the VL of P1-068767_D52N_D102V;
  • VH CDR1, CDR2 and CDR3 one or more of VH CDR1, CDR2 and CDR3 of:
  • an anti-VISTA Ab comprises any of the variable regions and/or variable region CDRs 1-3 of the antibodies described above and elsewhere herein, such as:
  • VH CDR1, CDR2 and CDR3 one or more of VH CDR1, CDR2 and CDR3 of:
  • hVISTA e.g., histidine rich region of the ECD or a
  • hVISTA e.g., histidine rich region of the ECD or a polypeptide comprising amino acid residues 35-127 of SEQ ID NO: 2, at
  • cyno VISTA e.g., histidine rich region of the ECD, at physiological pH or neutral pH, e.g., pH 7.4 or pH 7.0;
  • hVISTA e.g., na ⁇ ve or activated T cells
  • acidic pH e.g., pH 6.0 or pH 6.5
  • T cell activation by, e.g., enhancing T cell proliferation; enhancing IFN-g production from T cells; and/or stimulating T cell receptor mediated NF-kB signaling;
  • (ttt) a heavy chain comprising the amino acid sequence of the heavy chain of P1- 061029_Y32E_F100fE.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-061029_Y32E_F100fE;
  • a HC comprising the HC CDRs of the HC of P1-068759 and a LC comprising the LC CDRs of P1-068759 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068759.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068773 and a LC comprising the LC CDRs of P1-068773 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068773.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068775 and a LC comprising the LC CDRs of P1-068775 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068775.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-069063 and a LC comprising the LC CDRs of P1-069063 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-069063.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-069065 and a LC comprising the LC CDRs of P1-069065 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-069065.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-069067 and a LC comprising the LC CDRs of P1-069067 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-069067.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-069071 and a LC comprising the LC CDRs of P1-069071 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-069071.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-069073 and a LC comprising the LC CDRs of P1-069073 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-069073.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068736 and a LC comprising the LC CDRs of P1-068736 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068736.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068742 and a LC comprising the LC CDRs of P1-068742 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068742.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068744 and a LC comprising the LC CDRs of P1-068744 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068744.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068746 and a LC comprising the LC CDRs of P1-068746 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068746.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068748 and a LC comprising the LC CDRs of P1-068748 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068748.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068750 and a LC comprising the LC CDRs of P1-068750 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068750.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068754 and a LC comprising the LC CDRs of P1-068754 and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068754.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E55A.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E55A and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E55A.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_H100G.IgG1.3 and a LC comprising the LC CDRs of P1-068761_H100G and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_H100G.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E56N.IgG1.3 and a LC
  • a HC comprising the HC CDRs of the HC of P1-068761_E30D.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E30D and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E30D.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E30D_E55A.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E30D_E55A and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E30D_E55A.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068761_E56N_H100G.IgG1.3 and a LC comprising the LC CDRs of P1- 068761_E56N_H100G and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068761_E56N_H100G.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068761_E30D_H100G.IgG1.3 and a LC comprising the LC CDRs of P1- 068761_E30D_H100G and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068761_E30D_H100G.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E30D_E56N.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E30D_E56N and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E30D_E56N.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068761_E55A_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1- 068761_E55A_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068761_E55A_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_H100G_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068761_H100G_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_H100G_E100fF.IgG1.3, respectively; (ss) a HC comprising the HC CDRs of the HC of P1-068761_E30D_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E30D_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at
  • a HC comprising the HC CDRs of the HC of P1-068761_E56N_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E56N_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E56N_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E32Y.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E32Y and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E32Y.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E32Y_E55A.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E32Y_E55A and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E32Y_E55A.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E32Y_E56N.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E32Y_E56N and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E32Y_E56N.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068761_E30D_E32Y.IgG1.3 and a LC comprising the LC CDRs of P1-068761_E30D_E32Y and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068761_E30D_E32Y.IgG1.3, respectively; (yy) a HC comprising the HC CDRs of the HC of P1- 068761_E32Y_H100G.IgG1.3 and a LC comprising the LC CDRs of P1- 068761_E32Y_H100G and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%,
  • a HC comprising the HC CDRs of the HC of P1- 068761_E32Y_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1- 068761_E32Y_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068761_E32Y_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_D52N_D102V.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_D52N_D102V and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_D52N_D102V.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_D52N.IgG1.3 and a LC comprising the LC CDRs of P1-068767_D52N and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_D52N.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_D52N_E55A.IgG1.3 and a LC comprising the LC CDRs of P1-068767_D52N_E55A and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_D52N_E55A.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_E55A_D102V.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_E55A_D102V and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_E55A_D102V.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_D102V.IgG1.3 and a LC comprising the LC CDRs of P1-068767_D102V and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_D102V.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_E55A.IgG1.3 and a LC comprising the LC CDRs of P1-068767_E55A and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_E55A.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_E30D_D52N.IgG1.3 and a LC comprising the LC CDRs of P1-068767_E30D_D52N and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_E30D_D52N.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_E30D_D102V.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_E30D_D102V and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_E30D_D102V.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_E100fF_D102V.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_E100fF_D102V and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_E100fF_D102V.IgG1.3, respectively;
  • (lll)a HC comprising the HC CDRs of the HC of P1-068767_E55A_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068767_E55A_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_E55A_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_D52N_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_D52N_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_D52N_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-068767_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1-068767_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-068767_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 068767_E30D_E100fF.IgG1.3 and a LC comprising the LC CDRs of P1- 068767_E30D_E100fF and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 068767_E30D_E100fF.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1- 061029_F100fE_V102D.IgG1.3 and a LC comprising the LC CDRs of P1- 061029_F100fE_V102D and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1- 061029_F100fE_V102D.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-061029_F100fE.IgG1.3 and a LC comprising the LC CDRs of P1-061029_F100fE and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-061029_F100fE.IgG1.3, respectively;
  • a HC comprising the HC CDRs of the HC of P1-061029_V102D.IgG1.3 and a LC comprising the LC CDRs of P1-061029_V102D and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-061029_V102D.IgG1.3, respectively;
  • (sss) a HC comprising the HC CDRs of the HC of P1-061029_Y32E.IgG1.3 and a LC comprising the LC CDRs of P1-061029_Y32E and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-061029_Y32E.IgG1.3, respectively; or
  • (ttt)a HC comprising the HC CDRs of the HC of P1-061029_Y32E_F100fE.IgG1.3 and a LC comprising the LC CDRs of P1-061029_Y32E_F100fE and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the HC and LC of P1-061029_Y32E_F100fE.IgG1.3, respectively.
  • the HC and/or LC may differ from the sequence of each of the species (a) to (ttt) by the presence of 1, 2, 3, 4, or 5 amino acid substitutions, such as 1, 2, 3, 4, or 5 conservative substitutions.
  • the HC of P1-061029 or one of its progeny may comprise one or both of the K16R and T84A substitutions in the VH region of the HC (P1-061015 and its progeny already have an R and an A at those positions, respectively).
  • an anti-hVISTA Ab may comprise:
  • (x) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068738.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068738;
  • (gg) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068761_E55A.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A;
  • (nn) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068761_E30D_H100G.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_H100G;
  • (tt) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068761_E56N_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_E100fF;
  • (yy) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068761_E32Y_H100G.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_H100G;
  • (aaa) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_D52N_D102V.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_D102V;
  • (bbb) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_D52N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N;
  • (ccc) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_D52N_E55A.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E55A;
  • (ddd) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_E55A_D102V.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A_D102V;
  • ggg a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_E30D_D52N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D52N;
  • (jjj) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_E30D_E55A.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_E55A;
  • (nnn) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 068767_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E100fF;
  • (rrr) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 061029_V102D.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-061029_V102D;
  • (sss) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 061029_Y32E.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-061029_Y32E; or
  • (ttt) a heavy chain consisting of the amino acid sequence of the heavy chain of P1- 061029_Y32E_F100fE.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-061029_Y32E_F100fE,
  • the disclosure contemplates anti-VISTA mAbs comprising:
  • the antibody may comprise a different heavy chain constant region sequence, such as a human wild-type IgG1 constant region such as human IgG1 allotype f (IgG1f) (SEQ ID NO: 182), or a modified human IgG1 constant region such as IgG1.1f (SEQ ID NO: 183), or a modified human IgG1 constant region such as IgG1.P238K (SEQ ID NO: 184).
  • a human wild-type IgG1 constant region such as human IgG1 allotype f (IgG1f) (SEQ ID NO: 182)
  • a modified human IgG1 constant region such as IgG1.1f (SEQ ID NO: 183
  • a modified human IgG1 constant region such as IgG1.P238K
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70);
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-061015;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068757;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069061;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1- 068761_E56N_H100G;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E100fF;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1- 068767_D52N_D102V;
  • ccc a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1- 068767_D52N_E55A;
  • nn a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1- 068761_E30D_H100G;
  • (tt) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1- 068761_E56N_E100fF;
  • (bbb) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N; (ccc) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1- 068767_D52N_E55A;
  • (ddd) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1- 068767_E55A_D102V; (eee) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D102V;
  • ggg a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1- 068767_E30D_D52N;
  • nnn a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E100fF;
  • (sss) a heavy chain consisting of (i) the amino acid sequence of the VH of P1- 061029_Y32E and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-061029_Y32E; or
  • the disclosure contemplates anti-VISTA mAbs comprising:
  • a heavy chain consisting of the amino acid sequences of (i) a VH of (a) to (ttt) listed above, (ii) SEQ ID NO: 182, and (iii) a Lys residue, wherein the C-terminal amino acid of VH and the N-terminal amino acid of SEQ ID NO: 182 form a peptidic bond and wherein the C-terminal amino acid of SEQ ID NO: 182 is joined to the N-terminal of the Lys; and
  • VH and light chain amino acid sequences are chosen from the same antibody species from among (a) to (ttt) listed above.
  • Certain embodiments of this disclosure include anti-VISTA Abs comprising:
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70);
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-061015;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068757;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068759;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068763;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068765;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069059;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069061;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069063;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069065;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069069;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069077;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068736;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068738;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068740;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068742;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068748;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068752;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E55A_E56N;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E30D_E55A;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E56N_H100G;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E30D_H100G;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E30D_E56N;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E100fF;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E55A_E100fF;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_H100G_E100fF;
  • tt a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E56N_E100fF;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E32Y_E55A;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E32Y_E56N;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068761_E30D_E32Y;
  • ccc a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068767_D52N_E55A;
  • (ddd) a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1- 068767_E55A_D102V;
  • a heavy chain comprising (i) the amino acid sequence of the VH of P1- 068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D102V;

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BR112020019083-7A BR112020019083A2 (pt) 2018-03-21 2019-03-19 Anticorpos, ácido nucleico, composições, célula e métodos para preparar um anticorpo, para tratar câncer, para tratar uma doença infecciosa, para tratar uma inflamação, para a identificação de um anticorpo, para melhorar a eficácia antitumoral de um anticorpo, para melhorar a farmacocinética de um anticorpo, para selecionar um anticorpo, para melhorar a eficácia de anticorpos, para isolar anticorpos, para detectar vista em uma amostra e para tratar câncer
MX2020009786A MX2020009786A (es) 2018-03-21 2019-03-19 Anticuerpos de union a supresor de la activacion de celulas t que contiene el dominio variable de inmunoglobulina (vista) a ph acido.
EP19718001.1A EP3768716A1 (en) 2018-03-21 2019-03-19 Antibodies binding to vista at acidic ph
CA3092589A CA3092589A1 (en) 2018-03-21 2019-03-19 Antibodies binding to vista at acidic ph
US16/982,277 US20210017283A1 (en) 2018-03-21 2019-03-19 Antibodies Binding to Vista at Acidic pH
CN201980020908.XA CN111971304A (zh) 2018-03-21 2019-03-19 在酸性pH结合至VISTA的抗体
KR1020207029795A KR20200135421A (ko) 2018-03-21 2019-03-19 산성 pH에서 VISTA에 결합하는 항체
JP2020550642A JP7510879B2 (ja) 2018-03-21 2019-03-19 酸性ｐＨでＶＩＳＴＡに結合する抗体
PE2020001432A PE20210290A1 (es) 2018-03-21 2019-03-19 ANTICUERPOS DE UNION A VISTA A pH ACIDO
EA202092208A EA202092208A1 (ru) 2018-09-19 2019-03-19 АНТИТЕЛА, СВЯЗЫВАЮЩИЕСЯ С VISTA ПРИ КИСЛОТНОМ pH
AU2019239747A AU2019239747A1 (en) 2018-03-21 2019-03-19 Antibodies binding to VISTA at acidic pH
SG11202008593PA SG11202008593PA (en) 2018-03-21 2019-03-19 ANTIBODIES BINDING TO VISTA AT ACIDIC pH
IL277331A IL277331A (en) 2018-03-21 2020-09-14 Antibodies bind to VISTA at acidic pH
CONC2020/0012415A CO2020012415A2 (es) 2018-03-21 2020-10-02 Anticuerpos de unión a vista a ph ácido
JP2024000234A JP2024050577A (ja) 2018-03-21 2024-01-04 酸性ｐＨでＶＩＳＴＡに結合する抗体

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WO2020014327A3 (en) * 2018-07-11 2020-02-27 Five Prime Therapeutics, Inc. Antibodies binding to vista at acidic ph
WO2021055698A1 (en) * 2019-09-19 2021-03-25 Bristol-Myers Squibb Company Antibodies binding to vista at acidic ph
CN113322223A (zh) * 2021-06-03 2021-08-31 重庆市畜牧科学院 富硒酵母基因工程菌及其表面展示系统及其构建方法
WO2021142305A3 (en) * 2020-01-10 2021-09-23 Coimmune, Inc. Methods of treating tumors
US11306150B2 (en) 2017-01-11 2022-04-19 Bristol-Myers Squibb Company Method of identifying a P-selectin glycoprotein ligand-1 (PSGL-1) antagonist
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